Severe Bleeding Diathesis in Siblings with Platelet Dysfunction due to a Novel Nonsense RASGRP2 Mutation

• Main Authors: Julia Körholz, Nadja Lucas, Franziska Boiti, Karina Althaus, Oliver Tiebel, Mingyan Fang, Reinhard Berner, Min Ae Lee-Kirsch, Ralf Knöfler
• Format: Article
• Language: English
• Published: Georg Thieme Verlag KG 2020-10-01
• Series: TH Open
• Subjects: bleeding diathesis; platelet dysfunction; rasgrp2
• Online Access: http://www.thieme-connect.de/DOI/DOI?10.1055/s-0040-1718910

Next-generation sequencing is increasingly applied during the diagnostic work-up of patients with bleeding diathesis and has facilitated the diagnosis of rare bleeding disorders such as inherited platelet function disorders. Mutations in RAS guanyl releasing protein 2 (RasGRP2), also known as calcium- and diacylglycerol-regulated guanine nucleotide exchange factor I (CalDAG-GEFI), underlie a recently described platelet signal transduction abnormality. Here we present the case of a consanguineous family originating from Afghanistan with two siblings affected by recurrent severe mucocutaneous bleedings. Platelet function testing demonstrated a marked reduction of aggregation induced by collagen and adenosine diphosphate. Whole exome sequencing revealed a novel homozygous nonsense RASGRP2 mutation segregating with the bleeding disorder in the family.